Hyperoxia and pulmonary vascular injury in bronchopulmonary dysplasia: pathogenic mechanisms and emerging therapies—a systematic review

BACKGROUND: Bronchopulmonary dysplasia (BPD), a leading respiratory complication in preterm infants, is strongly associated with hyperoxia-induced pulmonary vascular injury resulting from essential oxygen therapy. The precise pathological mechanisms linking hyperoxia to BPD, along with effective interventions, remain poorly understood. This review systematically analyzes existing literature to elucidate these mechanisms and evaluate potential therapies, thereby informing future research directions. METHODS: A thorough search was conducted across electronic databases, including PubMed, Web of Science, and Embase. Literature up to August 2025 concerning hyperoxia and pulmonary vascular injury in both patients with BPD and animal models was reviewed. RESULTS: From 807 initial records, 359 remained after duplicate removal. Following eligibility screening, 55 articles were included for analysis. The vast majority were preclinical studies, with 32 focusing on disease mechanisms and 23 investigating potential treatments. CONCLUSION: Hyperoxia-induced pulmonary vascular injury in BPD is driven by a multifaceted network involving signaling pathways, epigenetic modifications, metabolic dysregulation, and phenotypic alterations, rather than a singular mechanism. Although emerging therapeutic strategies show promise and diversity, aligning with the complex etiology of BPD, the majority of interventions targeting pulmonary vascular injury remain at the preclinical stage. Advancing their clinical translation represents a key direction for future research. IMPACT: This review systematically synthesizes existing evidence, clarifies the central role of hyperoxia-induced pulmonary vascular injury in bronchopulmonary dysplasia, and further validates the vascular hypothesis. This review suggests that hyperoxia-induced pulmonary vascular injury is not attributable to a single cause, but a complex network of injury mechanisms, which is also consistent with the multifactorial pathogenesis of bronchopulmonary dysplasia. This review finds that the vast majority of current studies remain at the preclinical stage, and promising therapeutic strategies urgently need further clinical translation, which represents a key gap in this field. It points out the direction for future research. Graphical AbstractThe Injury-Mechanism-Intervention-Outcome Process of Hyperoxia-Induced Pulmonary Vascular Damage.